EPAS-1基因甲基化水平及蛋白表达与肾透明细胞癌临床特征的相关性  

Correlation of EPAS-1 gene methylation level and protein expression with clinical characteristics of renal clear cell carcinoma

作　　者：陈海滨[1] 赵建军[1] 程小龙 谭超 Chen Haibin;Zhao Jianjun;Cheng Xiaolong;Tan Chao(Second Department of Urology,Affiliated Hospital of Hebei Engineering University, Hebei Province,Handan 056004, China)

机构地区：[1]河北工程大学附属医院泌尿外二科,邯郸056004

出　　处：《疑难病杂志》2021年第11期1085-1089,共5页Chinese Journal of Difficult and Complicated Cases

基　　金：河北省卫生健康委员会资助项目(20200591);邯郸市科学技术研究与发展计划项目(19422083011-2)。

摘　　要：目的分析内皮PAS区域蛋白1(EPAS-1)基因甲基化及蛋白表达水平与肾透明细胞癌临床特征及预后的关系。方法选取2014年2月—2015年8月河北工程大学附属医院泌尿外二科诊治肾透明细胞癌患者86例的癌组织作为肾透明细胞癌组,癌旁正常组织作为癌旁对照组。亚硫酸氢钠处理基因组DNA后采用直接测序法检测组织EPAS-1基因甲基化水平,采用免疫组织化学法检测组织EPAS-1蛋白表达水平;分析肾透明细胞癌患者癌组织EPAS-1甲基化水平及蛋白表达与临床病理特征的关系;多因素Cox回归分析影响肾透明细胞癌预后的因素。结果肾透明细胞癌组EPAS-1基因甲基化率为62.79%(54/86),高于癌旁对照组的16.28%(14/86),差异有统计学意义(χ^(2)/P=38.914/0.000);肾透明细胞癌组EPAS-1蛋白表达阳性率23.26%(20/86),低于癌旁对照组的65.12%(56/86),差异有统计学意义(χ^(2)/P=30.553/0.000)。肿瘤≥4.0 cm、转移(Fuhrman)分级高级别肾透明细胞癌患者癌组织EPAS-1甲基化率高于肿瘤<4.0 cm、Fuhrman分级低级别患者(χ^(2)/P=10.261/0.001,9.097/0.003);蛋白表达阳性率低于肿瘤<4.0 cm、Fuhrman分级低级别患者(χ^(2)/P=10.402/0.001,4.160/0.041)。EPAS-1基因甲基化肾透明细胞癌患者5年生存率低于EPAS-1基因非甲基化患者(51.85%vs.78.13%,χ^(2)=5.865,P=0.015);EPAS-1蛋白阳性表达肾透明细胞癌患者5年生存率高于EPAS-1蛋白阴性表达(85.00%vs.54.55%,χ^(2)=6.020,P=0.014)。EPAS-1基因甲基化是影响肾透明细胞癌患者死亡的独立危险因素[OR(95%CI)=2.093(1.574~2.784)],EPAS-1蛋白阳性表达是其保护因素[OR(95%CI)=0.677(0.469~0.978)]。结论EPAS-1基因启动子高甲基化及蛋白低表达可能与肾透明细胞癌的发生、发展及预后有关。Objective To analyze the relationship between endothelial PAS domain protein 1(EPAS-1)gene methylation and protein expression levels and clinical characteristics and prognosis of renal clear cell carcinoma.Methods From February 2014 to August 2015,the cancer tissues of 86 patients with renal clear cell carcinoma diagnosed and treated in the Second Department of Urology,Affiliated Hospital of Hebei University of Technology were selected as the renal clear cell carcinoma group,and the adjacent normal tissues were used as the adjacent control group.After processing genomic DNA with sodium bisulfite,direct sequencing was used to detect the methylation level of the tissue EPAS-1 gene,and the immunohistochemistry method was used to detect the tissue EPAS-1 protein expression level.To analyze the relationship between the methylation level and protein expression of EPAS-1 in cancer tissues of patients with renal clear cell carcinoma and clinicopathological characteristics.Multivariate Cox regression analysis of factors affecting the prognosis of renal clear cell carcinoma.Results The methylation rate of EPAS-1 gene in the renal clear cell carcinoma group was 62.79%(54/86),which was higher than 16.28%(14/86)in the adjacent control group.The difference was statistically significant(χ^(2)/P=38.914/0.000).The positive rate of EPAS-1 protein expression in the renal clear cell carcinoma group was 23.26%(20/86),which was lower than 65.12%(56/86)in the adjacent control group.The difference was statistically significant(χ^(2)/P=30.553/0.000).The methylation rate of EPAS-1 in cancer tissues of patients with tumor≥4.0 cm and metastasis(Fuhrman)grade high-grade renal clear cell carcinoma was higher than that of patients with tumors<4.0 cm and Fuhrman grade low-grade patients(χ^(2)/P=10.261/0.001,9.097/0.003).The positive rate of protein expression was significantly lower than that of patients with tumors<4.0 cm and Fuhrman grade low-grade patients(χ^(2)/P=10.402/0.001,4.160/0.041).The 5-year survival rate of patients with EPAS

关 键 词：肾透明细胞癌 内皮PAS区域蛋白1 甲基化 预后 

分 类 号：R737.11[医药卫生—肿瘤]